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RV‐induced type 1 IFNs induce antiviral gene expression and apoptosis in intestinal epithelia
Author(s) -
Frias Amena Husain,
Jones Rheinallt,
VijayKumar Matam,
Gewirtz Andrew T.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.570.16
Subject(s) - irf7 , biology , apoptosis , immune system , innate immune system , interferon , virology , signal transduction , antibody , cytokine , stat1 , immunology , microbiology and biotechnology , biochemistry
Rotaviruses (RV) are the leading cause of diarrhea in children. RV primarily infects intestinal epithelial cells (IEC), which typically clear the infection within 7 days via an innate immune‐mediated mechanism. Type 1 IFNs (α/β) mediate various aspects of the immune response to a number of viruses in a variety of cell types. Thus, we sought to define whether RV induced type I IFN in IEC and determine the role of such IFN in the antiviral immune response. Intestinal epithelial cells (HT29) were infected with RV (MOI 1) alone or in the presence of neutralizing antibodies to IFN‐α/β. Viral protein synthesis, antiviral signaling (IRF7, STAT1, and PKR) and PARP cleavage (an apoptotic event) was detected by western blotting. Cell morphology was assessed by light microscopy. Type 1 IFN and IL‐8 (inflammatory cytokine) induction was measured by qRT‐PCR or ELISA. RV robustly induced IFN‐β, but not IFN‐α. In accordance, blockade of IFN‐β was without effect, while blockade of IFN‐β completely ablated the potent induction of p‐STAT1, p‐PKR and IRF7 induced by RV alone. IFN‐β blockade also resulted in modest suppression of viral protein expression. Most surprisingly, RV alone induced epithelial cytopathology/ apoptosis that was abrogated when IFN‐β activity was blocked. Thus, RV‐induced IFN‐β is essential for IEC antiviral signaling and may also promote viral replication and apoptosis of infected cells.